Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history

It has been 50 years since the initial descriptions of what are now known as plasmacytoid dendritic cells (pDC) and type I IFN. pDC, which are infrequent cells found in the peripheral blood and lymphoid organs, are the most potent producers of type I and type III IFNs in the body. pDC produce IFN-α in response to both DNA and RNA enveloped viruses by virtue of their ribonucleic acids signaling in the endosome through TLR9 and TLR7, respectively. This stimulation, which also occurs with DNA or RNA-containing immune complexes and synthetic TLR7 and -9 agonists, is dependent upon the transcription factor IRF-7, which is expressed at high constitutive levels in pDC. In addition to releasing as much as 3–10 pg of IFN-α/cell, pDC are also potent modulators of the immune response. In this review, we discuss the signaling pathways in pDC, their roles in linking innate and adaptive immunity, and their roles in infectious disease and autoimmunity.